A Study of Ruxolitinib in Combination With Corticosteroids for the Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease (REACH1)

Inclusion Criteria:

- Have undergone first allogeneic hematopoietic stem cell transplantation (allo-HSCT)
from any donor source using bone marrow, peripheral blood stem cells, or cord blood
for hematologic malignancies. Recipients of nonmyeloablative and myeloablative
conditioning regimens are eligible.

- Clinically suspected Grades II to IV acute GVHD as per MAGIC guidelines, occurring
after allo-HSCT with any conditioning regimen and any anti-GVHD prophylactic program.

- Subjects with steroid-refractory acute GVHD, defined as any of the following:

- Subjects with progressive GVHD (ie, increase in stage in any organ system or any
new organ involvement) after 3 days of primary treatment with methylprednisolone
≥ 2 mg/kg per day (or equivalent).

- Subjects with GVHD that has not improved (ie, decrease in stage in at least 1
involved organ system) after 7 days of primary treatment with methylprednisolone
≥ 2 mg/kg per day (or equivalent).

- Subjects who previously began corticosteroid therapy at a lower dose (at least 1
mg/kg per day methylprednisolone) but develop new GVHD in another organ system.

- Subjects who cannot tolerate a corticosteroid taper, that is, begin
corticosteroids at 2.0 mg/kg per day, demonstrate response, but progress before a
50% decrease from the initial starting dose of corticosteroids is achieved.

- Evidence of myeloid engraftment (eg, absolute neutrophil count ≥ 0.5 × 10^9/L for 3
consecutive days if ablative therapy was previously used). Use of growth factor
supplementation is allowed.

Exclusion Criteria:

- Has received more than 1 allo-HSCT.

- Has received more than 1 systemic treatment in addition to corticosteroids for acute
GVHD.

- Presence of GVHD overlap syndrome as per NIH guidelines.

- Presence of an active uncontrolled infection. An active uncontrolled infection is
defined as hemodynamic instability attributable to sepsis or new symptoms, worsening
physical signs, or radiographic findings attributable to infection. Persisting fever
without signs or symptoms will not be interpreted as an active uncontrolled infection.

- Known human immunodeficiency virus infection.

- Active hepatitis B virus (HBV) or hepatitis C virus infection that requires treatment
or at risk for HBV reactivation. Subjects whose immune status is unknown or uncertain
must have results confirming immune status before enrollment.

- Serum creatinine > 2.0 mg/dL or creatinine clearance < 40 mL/min measured or
calculated by Cockroft-Gault equation.

- Subjects with evidence of relapsed primary disease, or subjects who have been treated
for relapse after the allo-HSCT was performed.

- Unresolved toxicity or complications (other than acute GVHD) due to previous
allo-HSCT.

- Any corticosteroid therapy for indications other than GVHD at doses of
methylprednisolone or equivalent > 1 mg/kg per day within 7 days of enrollment.

- Severe organ dysfunction unrelated to underlying GVHD, including:

- Cholestatic disorders or unresolved veno-occlusive disease of the liver (defined
as persistent bilirubin abnormalities not attributable to GVHD and ongoing organ
dysfunction).

- Clinically significant or uncontrolled cardiac disease including unstable angina,
acute myocardial infarction within 6 months from Day 1 of study drug
administration, New York Heart Association Class III or IV congestive heart
failure, circulatory collapse requiring vasopressor or inotropic support, or
arrhythmia that requires therapy.

- Clinically significant respiratory disease that requires mechanical ventilation
support or 50% oxygen.

- Currently breast feeding.

- Received Janus kinase inhibitor therapy after allo-HSCT for any indication. Treatment
with a JAK inhibitor before allo-HSCT is permitted.

- Treatment with any other investigational agent, device, or procedure, within 21 days
(or 5 half-lives, whichever is greater) of enrollment. Subjects participating in a
GVHD prophylaxis study or conditioning regimen should be discussed with the sponsor's
medical monitor before enrollment.

- Any condition that would, in the investigator's judgment, interfere with full
participation in the study, including administration of study drug and attending
required study visits; pose a significant risk to the subject; or interfere with
interpretation of study data.

- Known allergies, hypersensitivity, or intolerance to any of the study medications,
excipients, or similar compounds.